PulseExploreJournal ClubDebatesTrendingResearchersJournals
Instagram
HomeExploreJournal ClubTrending
Synapse
⌘+K
Synapse
April 5, 2026Cancer Research0 citations

Abstract 7511: Extrachromosomal MDM2 amplifications define an ecDNA-permissive tumor cell state that impacts intercellular tumor heterogeneity and treatment response across cancers

View Full Paper
RSRachel SchmargonGMGiulia MontuoriERElias Rodríguez-Fos

Key Points

  • To explore how MDM2 ecDNA amplifications affect tumor heterogeneity and treatment responses in various cancers, particularly in TP53-wildtype tumors.
  • Integrated analysis of pan-cancer ecDNA reconstructions
  • Single-cell DNA and RNA sequencing
  • Acute drug treatment perturbations in cell lines and PDX models
  • Fluorescence-in-situ hybridization and immunofluorescence
  • MDM2 is the most frequently amplified oncogene across cancers on ecDNA.
  • MDM2 ecDNA is linked to increased copy number and complexity, especially in TP53-wildtype tumors.
  • Treatment responses varied significantly based on MDM2 ecDNA levels, impacting TP53 activity and cell survival.

Abstract

Abstract Extrachromosomal DNA (ecDNA) amplifies oncogenes with high copy-number variability, promoting heterogeneity, rapid tumor evolution and treatment failure. MDM2, a key negative regulator of TP53, is frequently amplified on ecDNA, yet its impact on ecDNA dynamics and ecDNA dosage-driven treatment responses remains unclear. We integrated pan-cancer ecDNA reconstructions (TCGA + PCAWG), single-cell DNA FISH and ImmunoFISH, scRNA-seq, scG Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7511.

Ask AI
Helpful
Bookmark
Share
View Full Paper

Cite This Study

Schmargon et al. (2026) studied this question.

synapsesocial.com/papers/69d1fdd4a79560c99a0a4224https://doi.org/10.1158/1538-7445.am2026-7511
Ask AI
Helpful
Bookmark
Share
View Full Paper